Signaling events in apoptotic photokilling of 5-aminolevulinic acid-treated tumor cells: Inhibitory effects of nitric oxide
Bhowmick, R; Girotti, AW
HERO ID
975868
Reference Type
Journal Article
Subtype
Abstract
Year
2008
Language
English
| HERO ID | 975868 |
|---|---|
| Material Type | Abstract |
| In Press | No |
| Year | 2008 |
| Title | Signaling events in apoptotic photokilling of 5-aminolevulinic acid-treated tumor cells: Inhibitory effects of nitric oxide |
| Authors | Bhowmick, R; Girotti, AW |
| Journal | Free Radical Biology and Medicine |
| Volume | 45 |
| Issue | Suppl. |
| Page Numbers | S28-S28 |
| Abstract | Photodynamic therapy (PDT) employs a photosensitizing agent, molecular oxygen, and visible light to produce reactive oxygen species that kill tumor and tumor vasculature cells in a sitespecific manner. Nitric oxide (NO) produced by these cells could be pro-carcinogenic by inhibiting apoptosis and promoting angiogenesis and tumor growth. We recently showed that NO from spermine NONOate (SPNO) or activated macrophages make COH-BR1 breast tumor cells hyperresistant to photokilling sensitized by 5-aminolevulinic acid (ALA)-generated protoporphyrin IX (PpIX). Signaling events associated with this hyperresistance are examined here. ALA-treated COH-BR1 cells containing mitochondria-localized PpIX were irradiated with broad-band visible light in the absence and presence of SPNO. Apoptotic vs. necrotic cell death was assessed by fluorescence microscopy. Redox signaling associated with MAP kinase (ERK1/2, p38, JNK) phosphorylation-activation and heme oxygenase-1 (HO-1) upregulation was studied using immunoprecipitation and Western blot methodology. Irradiation of sensitized cells resulted in activation of pro-apoptotic p38α and JNK with concomitant deactivation of pro-survival p38β and ERK1/2. NO delivered during irradiation had an anti-apoptotic effect accompanied by substantially greater HO-1 induction and reversal of the effects seen without NO. Downstream of MAPK activation, we observed induction of pro-apoptotic Bax and repression of anti-apoptotic Bcl-xL, both responses being reversed by NO. These findings provide new insights into signaling activity associated with the intrinsic apoptotic pathway in ALA-PDT and how this activity can be modulated by NO. (Supported by NIH: CA70823) |
| Wosid | WOS:000260867900068 |
| Url | http://www.sciencedirect.com/science/article/pii/S0891584908006205 |
| Is Certified Translation | No |
| Dupe Override | No |
| Conference Location | Indianapolis, IN |
| Conference Name | Society for Free Radical Biology and Medicine 15th Annual Meeting |
| Conference Date | November 19-23, 2008 |
| Is Public | Yes |
| Language Text | English |
| Relationship(s) |
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